期刊
ISCIENCE
卷 25, 期 10, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2022.105210
关键词
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资金
- Liechtenstein Government
- Swiss Heart Foundation
- Swiss Society of Hypertension
- University of Basel
- University Hospital Basel
- Hanela Foundation
- Mach-Gaensslen Foundation
- Schiller AG
- Novartis
- Swiss National Science Foundation [33CS30-177506/1, 33CS30-148470/1, 33CS30-148470/2, 33CSCO-134276/1, 33CSCO-108796, 324730_135673, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099, PMPDP3_129021/1, PMPDP3_141671/1]
- Federal Office for the Environment
- Federal Office of Public Health
- Federal Office of Roads and Transport
- canton government of Aargau
- canton government of Basel-Stadt
- canton government of Basel-Land
- canton government of Geneva
- canton government of Luzern
- canton government of Ticino
- canton government of Valais
- canton government of Zurich
- Swiss Lung League
- canton Lung League of Basel Stadt/Basel Landschaft
- canton Lung League of Zurich
- Stiftung ehemals Bundner Heilstatten
- SUVA
- Freiwillige Akademische Gesellschaft
- UBS Wealth Foundation
- Talecris Biotherapeutics GmbH
- Abbott Diagnostics
- Klinik Barmelweid
- Hirslanden Klinik Aarau
- European Commission [018996]
- Wellcome Trust [WT 084703MA]
- Exposomics EC FP7 grant [308610]
- National Heart, Lung, and Blood Institute (NHLBI)
- NHLBI [N02-HL-64278, HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086]
- National Institute of Neurological Disorders and Stroke (NINDS)
- National Institute on Aging (NIA) [R01AG023629]
- National Center for Advancing Translational Sciences, CTSI [UL1TR001881]
- National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) [DK063491]
- Laughlin Family
- NIH/NHLBI [R01HL141881]
- canton Lung League of Geneva
- canton Lung League of Ticino
- canton Lung League of Valais
- canton Lung League of Graubunden
- National Heart, Lung, and Blood Institute [75N92021D00006, U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, U01HL130114, HL130114, R01HL141989]
- [75N92020D00001]
- [HHSN268201500003I]
- [N01-HC-95159]
- [75N92020D00005]
- [N01-HC-95160]
- [75N92020D00002]
- [N01-HC-95161]
- [75N92020D00003]
- [N01-HC-95162]
- [75N92020D00006]
- [N01-HC-95163]
- [75N92020D00004]
- [R01 HL127659]
- [N01-HC-95164]
- [75N92020D00007]
- [N01-HC-95165]
- [N01-HC-95166]
- [N01-HC-95167]
- [N01-HC-95168]
- [N01-HC-95169]
- [UL1-TR-000040]
- [UL1-TR-001079]
- [UL1-TR-001420]
- [UL1-TR-001881]
- Swiss National Science Foundation (SNF) [33CS30_177506] Funding Source: Swiss National Science Foundation (SNF)
This study identified a significant genetic locus at the SCN5A gene associated with PAC frequency. Additionally, there was a significant concordance of effect between PAC frequency and genetic variants previously associated with AF. However, not all AF risk loci were associated with PAC frequency.
Premature atrial contractions (PACs) are frequently observed on electrocardiograms and are associated with increased risks of atrial fibrillation (AF), stroke, and mortality. In this study, we aimed to identify genetic susceptibility loci for PAC frequency. We performed a genome-wide association study meta-analysis with PAC frequency obtained from ambulatory cardiac monitoring in 4,831 individuals of European ancestry. We identified a genome-wide significant locus at the SCN5A gene. The lead variant, rs7373862, located in an intron of SCN5A, was associated with an increase of 0.12 [95% CI 0.08-0.16] standard deviations of the normalized PAC frequency per risk allele. Among genetic variants previously associated with AF, there was a significant enrichment in concordance of effect for PAC frequency (n = 73/106, p = 5.1310(-5)). However, several AF risk loci, including PITX2, were not associated with PAC frequency. These findings suggest the existence of both shared and distinct genetic mechanisms for PAC frequency and AF.
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